Oral Candidiasis - Widely Prevalent, Frequently Missed
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Oral Candidiasis - Widely Prevalent, Frequently Missed
DOI: 10.17354/ijss/2015/421 R eview A r ti c l e Oral Candidiasis - Widely Prevalent, Frequently Missed Pankaj Rathod1, Rohit Punga2, Vipinder Dalal3, Dhananjay Rathod4 1 Senior Lecturer, Department of Oral Surgery, PDM Dental College and Research Centre, Bahadurgarh, Haryana, India, 2Reader, Department of Oral Surgery, PDM Dental College and Research Centre, Bahadurgarh, Haryana, India, 3Senior Consultant, Department of Dental Surgery, General Hospital, Bahadurgarh, Haryana, India, 4Post-graduate Student, Department of Orthodontics, Seema Dental College and Hospital, Rishikesh, Uttarakhand, India Abstract A Candidiasis describes a group of yeast-like fungal infections involving the skin and mucous membranes. Infection is caused by Candida species, typically, Candida albicans. The candidiasis is seen orally in people with altered oral ecology (from dental appliances, hyposalivation, or the use of immunosuppressants or antimicrobials) and/or impaired immunity (e.g., transplant recipients, persons on immunosuppressive treatments, persons with HIV/AIDS, or other cellular immune defects). With the high prevalence and opportunistic nature, it is one of the most common infections found in the oral cavity, especially in the geriatric population. Due to asymptomatic nature of the infection and clinicians negligence during the examination, it is one of the frequently missed pathology. The purpose of this study is to enumerate in detail the various types, epidemiology, and management of oral candidiasis. Key words: Candidiasis, Cheilitis, Erythema, Immunology, Leukemia, Pemphigoid, Stomatitis, Squamous cell carcinoma INTRODUCTION The candidiasis is an opportunistic infection commonly affecting the oral cavity. It is often undiagnosed among elderly, particularly in denture wearers and in many cases is avoidable with proper oral hygiene care. It can also be a mark of systemic diseases, such as diabetes mellitus and is a common problem among the immunocompromised.1 The candidiasis of the oral cavity is caused due to overgrowth or infection by a yeast-like fungi, Candida.2,3 The predominant ones are Candida albicans (the commonest), Candida tropicalis, Candida glabrata, Candida guilliermondii, Candida pseudotropicalis, Candida krusei, Candida lusitaniae, Candida parapsilosis, and Candida stellatoidea. C. albicans, C. glabrata, and C. tropicalis represent more than 80% of isolates from clinical infection.4 The oral candidiasis is the most common human fungal infection especially in Access this article online Month of Submission : 07-2015 Month of Peer Review : 08-2015 Month of Acceptance : 08-2015 Month of Publishing : 09-2015 www.ijss-sn.com early and later life.5,6 In the general population, carriage rates have been found to range from 20% to 75% without any symptoms.5 The incidence of candidiasis in the oral cavity with predominant C. albicans isolation has been reported to be 45% in neonates.7 45-65% in childrens,8 30-45% of healthy adults,9 50-65% in cases of long-term denture wearers,10 65-88% in those residing in acute and long-term facilities,11-13 90% in patients with acute leukemia undergoing chemotherapy,14 and 95% of patients with HIV infection.15 C. albicans is a normal commensal of the oral cavity and is usually asymptomatic in healthy individuals. However, extensive overgrowth of the fungi can sometimes lead to symptoms such as altered taste sensation, local discomfort, and occasionally dysphagia. Systemic candidiasis carries a mortality rate of 71-79%.16 It is important for all the clinicians treating the older patients to be aware of the risk factors, diagnosis, and treatment of oral candidiasis. In a recent study, it was found that 30% of clinicians agreed that, even without examining the oral cavity, they would prescribe nystatin for oral candidiasis on the request of assistant staff.17 Such negligence can lead to an inaccurate diagnosis, missed pathologies, and failure to address the risk factors which may lead to recurrence of candidiasis. Corresponding Author: Dr. Pankaj Rathod, Department of Oral Surgery, PDM Dental College and Research Centre, Sarai Aurangabad, Jajjhar, Bahadurgarh - 124 507, Haryana, India. Phone: +91-9992029736/9354845574. E-mail: pankajr1982@rediffmail.com 193 International Journal of Scientific Study | September 2015 | Vol 3 | Issue 6 Rathod, et al.: Oral Candidiasis - Widely Prevalent, Frequently Missed CLASSIFICATION AND TYPES There are different types of oropharyngeal candidiasis including acute pseudomembranous, acute atrophic, chronic hyperplastic, denture stomatitis, median rhomboid glossitis, and angular cheilitis.18 Acute Pseudomembranous Candidiasis (Thrush) They commonly occur as adherent white plaques resembling curdled milk or cottage cheese on the surface of the labial and buccal mucosae, hard and soft palates, tongue, periodontal tissues, and oropharynx. The membrane can be scrapped off with a swab to expose the underlying erythematous mucosa (Figure 1). It is often easily diagnosed and is one of the commonest forms of oropharyngeal candidiasis accounting for almost a third.19 The diagnosis can be confirmed microbiologically either by culturing a swab from an oral rinse or by staining a smear from the affected area. Histologically, it is characterized by extensive white pseudomembranes consisting of desquamated epithelial cells, fibrin, and fungal hyphae. Predisposing factors include debilitating diseases such as diabetes mellitus, extremes of age, HIV infections, leukemias, those under steroid therapy, antibiotics or psychotropic drugs, and terminally ill patients. Figure 1: Pseudomembranous candidiasis involving the dorsal surface of tongue Acute Atrophic Candidiasis Acute atrophic candidiasis also known as erythematous candidiasis is commonly associated with burning sensations in the oral cavity or the tongue. Clinical appearance of white flecks may not be the prominent feature. The tongue may appear to be bright red or even give a bald appearance. The diagnosis may be sometimes difficult and should be considered in the differential diagnosis of a sore tongue, especially in a long-term denture wearing old patient who has received antibiotic therapy or who is on inhaled steroids. A swab from the affected area usually helps in confirming the diagnosis. Figure 2: Hyperplastic candidiasis involving the right lateral border of tongue Chronic Hyperplastic Candidiasis It characteristically occurs on the buccal mucosa or lateral border of the tongue as a speckled or homogenous white lesion (Figure 2). It is usually associated with smoking, and complete resolution of the infection seems to be dependent on cessation of the habit.20 This condition can progress to severe dysplasia or malignancy and is also referred to as Candidal leukoplakia (Figure 3). Candida species may not always be isolated from the lesions of oral leukoplakia, and their presence in these premalignant lesions may be suggestive of a complicating factor rather than a causative one.21 This condition may be confused with lichen planus, pemphigus or pemphigoid, or squamous cell carcinoma. Figure 3: Candidal leukoplakia involving the left commissural region Denture Stomatitis This condition is characterized by a localized chronic erythema of tissues in a denture wearing area. Lesions usually occur on the palate and upper jaw but may also International Journal of Scientific Study | September 2015 | Vol 3 | Issue 6 194 Rathod, et al.: Oral Candidiasis - Widely Prevalent, Frequently Missed affect the mandibular tissues (Figure 4). It is quite a common lesion with a high incidence rate of up to 65%. Median Rhomboid Glossitis It occurs as a chronic symmetrical lesion on the tongue anterior to circumvallate papillae. It is made up of atrophic filiform papillae. The presence of Candida is detected in more than 85% of the cases in a biopsy of this area.22 It is often associated with smoking and the use of inhaled steroids. Angular Cheilitis It is an erythematous fissuring at one or both corners of the mouth, usually associated with an intraoral candidal infection. Other organisms implicated are staphylococci and streptococci. In case of staphylococci, the reservoir is commonly in the anterior region of the nostrils and spreads to the angle of mouth which has been confirmed by phage typing.23,24 Facial wrinkling at the corners of the mouth and along the nasolabial fold, especially in older persons, leads to a chronically moist environment that predisposes to this lesion.25 This wrinkling is even worse in long-term denture wearers, as resorption of the alveolar ridges leads to a reduction in height of the lower face when the mouth is closed.26 Other factors implicated in the etiology of this condition are iron deficiency anemia and vitamin B12 deficiency. Chronic Mucocutaneous Candidiasis It describes a group of rare syndromes, which sometimes include a definable immune defect, in which persistent mucocutaneous candidiasis response is extremely poor to topical anti-fungal treatment. Recent studies have shown defect in cytokine (interleukine 2 and interferon-g) production with reduced lymphocyte function (TH1 and TH2) activity in response to candidal and few bacterial antigens. PATHOPHYSIOLOGY C. albicans is the predominant causal organism of most types of candidiasis. It is a relatively harmless organism inhabitating the oral cavity of almost 50% of the population. Other species including C. krusei, have been found in immunocompromised persons. C. glabrata is an emerging cause of oropharyngeal candidiasis in patients receiving radiation for head and neck cancer.27 In patients with HIV infection, new species, such as Candida dubliniensis and Candida inconspicua, have been recognized. EPIDEMIOLOGY Frequency The candidiasis is common in groups at risk, such as patients who are immunocompromised. Incidence of infection is rising, primarily because of HIV infection and both increase in candidal species and resistance to antifungals.28 Sex The candidiasis is reported to occur with equal frequency in both the sexes worldwide, except in areas where males with HIV infection outnumber females. Age The candidiasis predominantly occurs in the older-aged persons; however, it is primarily seen in the third and fourth decades of life in those with HIV infections. Mortality The candidiasis may occasionally predispose to esophageal spread that may prove to be life-threatening.29 HISTOPATHOLOGY Histologically, an increase thickness of the parakeratin layer with elongated rete ridges are seen. The candidal hyphae infiltrate the parakeratin layer and rarely penetrate into the cell layers of infected epithelium. Chronic inflammatory cell infiltrate in the connective tissue with neutrophilic microabscesses in the parakeratin layer is a prominent feature (Figure 5).30 MANAGEMENT Taking a history followed by a thorough examination of the oral cavity, including the hard and soft palates, the buccal mucosae are usually good starting points. In case of denture wearers, the examination should be done after they have been removed. Predisposing factors should be identified and resolved followed by an assessment of the type, severity, and chronicity of the infection. Figure 4: Denture stomatitis 195 The correct diagnosis can be reached based on the finding of characterized lesion, ruling out the other possibilities, International Journal of Scientific Study | September 2015 | Vol 3 | Issue 6 Rathod, et al.: Oral Candidiasis - Widely Prevalent, Frequently Missed Topical Antifungal Therapy Figure 5: Histopathology showing tubular hyphae of Candida albicans embedded in the parakeratin layer (Periodic acid-Schiff stain) and assessing the response to antifungal treatment. Acute pseudomembranous and chronic atrophic candidiasis can be treated based on the clinical features, however when the initial therapy is not successful, culture and sensitivity testing can be undertaken. Imprint cultures,6 have also been used for identification of Candida species, where sterile foams dipped in Sabouraud’s broth are placed for 30 s on the lesion, and then for an hour in Sabouraud’s agar containing chloramphenicol, after which they are incubated. Acute atrophic and chronic hyperplastic types may mimic other lesions and to rule out any kind of malignancy, a biopsy is recommended in addition to the empirical therapy. The oral hygiene maintenance and topical antifungals are usually adequate for uncomplicated forms of oral candidiasis.31 The oral hygiene involves scaling of teeth and regular cleaning dentures. Dentures should be cleaned and disinfected daily and left out overnight or at least 6 h daily. The dentures soaked in a denture cleaning solution such as chlorhexidine has been found to be very effective in eliminating Candida than brushing.32 This is because the porous and irregular surfaces of the dentures on which the Candida can easily adhere, cannot be removed by brushing alone. When rinsing the mouth with topical antifungal, the patient should ensure that the dentures are removed and that the entire oral mucosa is coated with antifungal and held in the mouth for a few minutes. The incorporation of an antifungal with a denture liner is recommended for patients with denture wearers. Furthermore, the mucosal surfaces should regularly be brushed using a soft brush. After disinfection, dentures should be allowed to air dry as this also kills adherent Candida on dentures.33 Chlorhexidine can discolor both dentures and natural dentition if not removed adequately after disinfection. Other denture cleaning methods, like ultrasonic cleaning tanks using a suitable solution, are not routinely used but found to be effective.34 Use of topical antifungal therapy is the first line treatment for uncomplicated oral candidiasis. In cases where systemic treatment is essential, topical therapy should continue, as this reduces the dose and duration of systemic treatment required.35-37 The adverse effects and drug interactions are more likely to occur with systemic agents than with topical agents. In the early part of 20th century, gentian violet, an aniline dye was used for the treatment of candidiasis. However, because of its limitations such as staining of the oral mucosa and the developing resistance, polyene antibiotics such as nystatin (1951) and amphotericin B (1956) were introduced. They act by binding to the cell membrane sterols of the fungi, thereby altering the cell membrane permeability.38,39 Nystatin and amphotericin are not absorbed from the gastrointestinal tract. Whereas other drugs such as miconazole, clotrimazole, or ketoconazole, used for the topical application have side effects such as vomiting and diarrhea. Nystatin is the most widely used topical agent for the treatment of oral candidiasis.2,3 It is available as an oral rinse, pastille, and suspension. The oral rinse contains sucrose and is found to be very useful in patients with HIV infections and also in completely edentulous patients. The clotrimazole troche can be an alternative to nystatin suspensions for those patients who find it unpalatable. Systemic Antifungal Therapy This therapy is appropriate in patients intolerant of or refractory to topical treatment and those at the high risk of developing systemic infections.40 Both nystatin oral rinses and clotrimazole troches have high levels of sucrose content and in diabetic or immunocompromised patients or in the presence of decayed teeth, triazoles such as fluconazole or itraconazole have been found to be effective.41 The ketoconazole has also been found to be equally effective, but its use is not recommended in elderly patients, due to drug interactions and side effects which include hepatotoxicity. The fluconazole is a potent and selective inhibitor of fungal enzymes which are involved in the synthesis of ergosterol. It disrupts cell wall formation followed by leakage of cellular contents and ultimately resulting in cell death. It is well absorbed by the gastrointestinal tract and does not produce side-effects such as hepatotoxicity. It is now listed in the dental practitioners’ formulary as well as the British National Formulary and is widely used both the practices. Itraconazole has a wider spectrum of activity than fluconazole, and is, therefore, valuable, in the treatment of candidiasis in immunocompromised patients who are resistant to fluconazole. Resistance to antifungals has International Journal of Scientific Study | September 2015 | Vol 3 | Issue 6 196 Rathod, et al.: Oral Candidiasis - Widely Prevalent, Frequently Missed become increasingly common since the introduction of fluconazole especially in patients with advanced HIV disease and recurrent and long-term treatment.42,43 Topical antifungal steroid creams and ointments are recommended for the treatment of angular cheilitis. Any concurrent intraoral lesions should also be treated at the same time, dietary deficiencies should be excluded and treated if found. Failure to respond to therapy especially in chronic atrophic candidiasis is usually due to noncompliance with the treatment. In patients undergoing treatment for cancers, oral prophylaxis with antifungal agents reduces the incidence of oral candidiasis, and in such cases, fluconazole have been found to be more effective than topical polyenes. Similar therapy has also been found to be effective in patients with HIV infections. asymptomatic and rarely produce any problem to the patients, and hence, often missed during routine clinical examination. Obtaining a thorough history and identifying the underlying cause are the first step toward successful management. The treating practitioner should have a complete knowledge about the dosage, actions and sideeffects of antifungal agents used for the treatment. Hence, it is important for all the clinicians, not to miss the candidal infection during routine examinations, and treat them appropriately. REFERENCES 1. 2. 3. PROGNOSIS 4. The prognosis for oral candidiasis is good with appropriate and effective treatment. Relapse, when it occurs is more often due to, inability to resolve the underlying or predisposing cause of infection, poor compliance with the therapy and failure to remove and clean dentures appropriately, in case of denture wearers. 5. DISCUSSION 9. Infection with the yeast-like fungal organism C. albicans is termed as candidiasis or candidosis. C. albicans is the primary organism causing the infection, although another member of the Candida genus, such as C. tropicalis, C. krusei, C. parapsilosis, and C. guilliermondii, may be also found intraorally, but very rarely cause the disease. Candida species are a routine component of the normal oral microflora. Factors such as systemic diseases, habits such as smoking, tobacco chewing, and long-term denture use, predispose to candidal infections. Clinically, candidiasis may present as white irregular flecks to severe erythematous patches. They commonly occur in older patients, but of late, their incidence is increasing in the third and fourth decades of life. The diagnosis is usually confirmed by taking a swab culture or biopsy of the affected area if required. Management of candidiasis includes identifying and removing the predisposing factors, use of antifungal therapy, good oral hygiene maintenance, and long-term follow-up. CONCLUSION 7. 8. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. The candidiasis is of various types affecting different regions in and around the oral cavity. They are usually 197 6. 22. Boriollo MF, Bassi RC, dos Santos Nascimento CM, Feliciano LM, Francisco SB, Barros LM, et al. Distribution and hydrolytic enzyme characteristics of Candida albicans strains isolated from diabetic patients and their non-diabetic consorts. Oral Microbiol Immunol 2009;24:437-50. Epstein JB. Antifungal therapy in oropharyngeal mycotic infections. Oral Surg Oral Med Oral Pathol 1990;69:32-41. Guida RA. Candidiasis of the oropharynx and esophagus. Ear Nose Throat J 1988;67:832, 834-6, 838-40. Ghannoum MA, Radwan SS. Candida Adherence to Epithelial Cells. Boca Raton, FL: CRC Press; 1990. Abu-Elteen KH, Abu-Alteen RM. The prevalence of Candida albicans populations in the mouths of complete denture wearers. New Microbiol 1998;21:41-8. Manning DJ, Coughlin RP, Poskitt EM. Candida in mouth or on dummy? Arch Dis Child 1985;60:381-2. Berdicevsky I, Ben-Aryeh H, Szargel R, Gutman D. Oral Candida in children. Oral Surg Oral Med Oral Pathol 1984;57:37-40. Lucas VS. Association of psychotropic drugs, prevalence of denturerelated stomatitis and oral candidosis. Community Dent Oral Epidemiol 1993;21:313-6. Arendorf TM, Walker DM. The prevalence and intra-oral distribution of Candida albicans in man. Arch Oral Biol 1980;25:1-10. Aldred MJ, Addy M, Bagg J, Finlay I. Oral health in the terminally ill: A cross-sectional pilot survey. Spec Care Dentist 1991;11:59-62. Cumming CG, Wight C, Blackwell CL, Wray D. Denture stomatitis in the elderly. Oral Microbiol Immunol 1990;5:82-5. Holbrook WP, Hjorleifsdottir DV. Occurrence of oral Candida albicans and other yeast-like fungi in edentulous patients in geriatric units in Iceland. Gerodontics 1986;2:153-6. Rodu B, Carpenter JT, Jones MR. The pathogenesis and clinical significance of cytologically detectable oral Candida in acute leukemia. Cancer 1988;62:2042-6. Dupont B, Graybill JR, Armstrong D, Laroche R, Touzé JE, Wheat LJ. Fungal infections in AIDS patients. J Med Vet Mycol 1992;30 Suppl 1:19-28. Fraser VJ, Jones M, Dunkel J, Storfer S, Medoff G, Dunagan WC. Candidemia in a tertiary care hospital: Epidemiology, risk factors, and predictors of mortality. Clin Infect Dis 1992;15:414-21. Morgan R, Tsang J, Harrington N, Fook L. Survey of hospital doctors’ attitudes and knowledge of oral conditions in older patients. Postgrad Med J 2001;77:392-4. Lewis MA, Lamey PJ. Clinical Oral Med. Oxford: Butterworth-Heinemann; 1995. Samaranayake LP. Nutritional factors and oral candidosis. J Oral Pathol 1986;15:61-5. Silverman S Jr, Luangjarmekorn L, Greenspan D. Occurrence of oral Candida in irradiated head and neck cancer patients. J Oral Med 1984;39:194-6. Dreizen S. Oral candidiasis. Am J Med 1984;77:28-33. Budtz-Jörgensen E. Etiology, pathogenesis, therapy, and prophylaxis of oral yeast infections. Acta Odontol Scand 1990;48:61-9. Kanbe T, Li RK, Wadsworth E, Calderone RA, Cutler JE. Evidence for expression of the C3d receptor of Candida albicans in vitro and in vivo International Journal of Scientific Study | September 2015 | Vol 3 | Issue 6 Rathod, et al.: Oral Candidiasis - Widely Prevalent, Frequently Missed 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. obtained by immunofluorescence and immunoelectron microscopy. Infect Immun 1991;59:1832-8. MacFarlane TW, Helnarska SJ. The microbiology of angular cheilitis. Br Dent J 1976;140:403-6. Shay K, Truhlar MR, Renner RP. Oropharyngeal candidosis in the older patient. J Am Geriatr Soc 1997;45:863-70. Penhall B. Preventive measures to control further bone loss and soft tissue damage in denture wearing. Aust Dent J 1980;25:319-24. Mandell GL, Bennet JE, Dolin R. Anti-fungal agents. Principles and Practice of Infectious Diseases. 4th ed. New York: Churchill Livingstone; 1994. p. 401-10. Redding SW, Dahiya MC, Kirkpatrick WR, Coco BJ, Patterson TF, Fothergill AW, et al. Candida glabrata is an emerging cause of oropharyngeal candidiasis in patients receiving radiation for head and neck cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;97:47-52. Lafleur MD, Qi Q, Lewis K. Patients with long-term oral carriage harbor high-persister mutants of Candida albicans. Antimicrob Agents Chemother 2010;54:39-44. Sitheeque MA, Samaranayake LP. Chronic hyperplastic candidosis/ candidiasis (candidal leukoplakia). Crit Rev Oral Biol Med 2003;14:253-67. Golecka M, Oldakowska-Jedynak U, Mierzwinska-Nastalska E, Adamczyk-Sosinska E. Candida-associated denture stomatitis in patients after immunosuppression therapy. Transplant Proc 2006;38:155-6. Tanida T, Okamoto T, Okamoto A, Wang H, Hamada T, Ueta E, et al. Decreased excretion of antimicrobial proteins and peptides in saliva of patients with oral candidiasis. J Oral Pathol Med 2003;32:586-94. Odman PA. The effectiveness of an enzyme-containing denture cleanser. Quintessence Int 1992;23:187-90. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. Stafford GD, Arendorf T, Huggett R. The effect of overnight drying and water immersion on candidal colonization and properties of complete dentures. J Dent 1986;14:52-6. Gwinnett AJ, Caputo L. The effectiveness of ultrasonic denture cleaning: A scanning electron microscope study. J Prosthet Dent 1983;50:20-5. Barkvoll P, Attramadal A. Effect of nystatin and chlorhexidine digluconate on Candida albicans. Oral Surg Oral Med Oral Pathol 1989;67:279-81. Barkvoll P, Hurlen B. Conventional treatment of oral candidiasis--new aspects. Nor Tannlaegeforen Tid 1989;99:116-9. Epstein JB, Polsky B. Oropharyngeal candidiasis: A review of its clinical spectrum and current therapies. Clin Ther 1998;20:40-57. Gupta AK, Sauder DN, Shear NH. Antifungal agents: An overview. Part I. J Am Acad Dermatol 1994;30:677-98. Bennet JE. Antimicrobial agents, Antifungal agents. In: Gilman AG, Rall TW, Nies AS, editors. Goodman and Gilman’s the Pharmacological Basis of Therapeutics. 8th ed. New York: Pergamon Press; 1990. p. 1165-81. Epstein JB, Freilich MM, Le ND. Risk factors for oropharyngeal candidiasis in patients who receive radiation therapy for malignant conditions of the head and neck. Oral Surg Oral Med Oral Pathol 1993;76:169-74. Blatchford NR. Treatment of oral candidosis with itraconazole: A review. J Am Acad Dermatol 1990;23:565-7. Heinic GS, Stevens DA, Greenspan D, MacPhail LA, Dodd CL, Stringari S, et al. Fluconazole-resistant Candida in AIDS patients. Report of two cases. Oral Surg Oral Med Oral Pathol 1993;76:711-5. Rex JH, Rinaldi MG, Pfaller MA. Resistance of Candida species to fluconazole. Antimicrob Agents Chemother 1995;39:1-8. How to cite this article: Rathod P, Punga R, Dalal V, Rathod D. Oral Candidiasis - Widely Prevalent, Frequently Missed. Int J Sci Stud 2015;3(6):193-198. Source of Support: Nil, Conflict of Interest: None declared. 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